Environmental impact of an anthropogenic groundwater temperature hotspot.

Heat emitted by buildings and other infrastructure accumulates in the subsurface. This additional heat can cause a pronounced shift in thermal boundary conditions of the important groundwater ecosystem. Shallow groundwater systems in Central Europe are often inhabited by communities of fauna adapted to cold and stable conditions as well as microorganisms, whose activity is dependent on ambient temperatures.

Preparation of von Hippel-Lindau (VHL) E3 ubiquitin ligase ligands exploiting constitutive hydroxyproline for benzylic amine protection.

The von Hippel-Lindau (VHL) protein serves as the substrate recognition subunit of the multi-subunit Cullin-2 RING E3 ubiquitin ligase (CRL2), which regulates intracellular concentrations of hypoxia inducible factors (HIFs) through a ubiquitin proteasome system (UPS) cascade. Strategic recruitment of CRL2 by bi- or trifunctional targeted protein degraders (, PROTACs®) offers the prospect of promoting aberrant polyubiquitination and ensuing proteasomal degradation of disease-related proteins. Non-peptidic, l-hydroxyproline-bearing VHL ligands such as VH032 (1) and its chiral benzylic amine analog Me-VH032 (2), are functional components of targeted protein degraders commonly employed for this purpose.

Cathepsin B Processing Is Required for the Efficacy of Albumin-Drug Conjugates.

Targeted drug delivery approaches that selectively and preferentially deliver therapeutic agents to specific tissues are of great interest for safer and more effective pharmaceutical treatments. We investigated whether cathepsin B cleavage of a valine-citrulline [VC()]-containing linker is required for the release of monomethyl auristatin E (MMAE) from albumin-drug conjugates. In this study, we used an engineered version of human serum albumin, Veltis High Binder II (HBII), which has enhanced binding to the neonatal Fc (fragment crystallizable) receptor (FcRn) to improve drug release upon binding and FcRn-mediated recycling.

The development and validation of the S-scan-parental self-management support (S-scan - PS): A self-reflection tool for child healthcare professionals.

Background: Professionals providing self-management support to parents regarding the care for their child with a chronic condition nowadays is an important aspect of child healthcare. This requires professionals to orient themselves towards partnership and collaboration with parents. The aims of the current study were the development and validation of the S-Scan-Parental self-management Support (S-scan - PS) as a tool for healthcare professionals to reflect on their attitude and practices regarding the support for parental self-management.

A low-cost alternative method of generating fibronectin micropatterned lines for cellular applications.

The cellular microenvironment contributes to the architecture, differentiation, polarity, mechanics and functions of the cell [1]. Spatial confinement of cells using micropatterning techniques allows to alter and regulate the cellular microenvironment for a better understanding of cellular mechanisms [2]. However, commercially available micropatterned consumables such as coverslips, dishes, plates etc.